The objective of this proposed research plan is to develop a widespread clinical agent for detecting myocardial metabolic changes in patients using single photon emission computed tomography and technetium99m labeled fatty acids proposed in this application. The proposed research will determine the optimal structure features of technetium-99m labeled fatty acid for the development of a myocardial imaging agent for nuclear medicine. Tc-99m-labeled fatty acids will be synthesized and their myocardium uptake studied in rats. Three series of fatty acids labeled with Tc-99m at different positions with respect to the lipophilic and carboxylic sites will be prepared and their chemical structure identified by preparation of their rhenium analogs. These fatty acid analogs utilize both the 1,2-dithia-5,8-diazacyclodecan and the '3+1' principle as the technetium chelating moieties. They are designed to be transported into myocardial cells by the long chain fatty acid carrier protein mechanism used by natural fatty acids. The fatty acid derivatives will be designed such that they cannot be completely catabolized. In this manner transport/delivery and metabolism can be imaged after the tracer is 'trapped' intracellularly. These studies will determine the potential of this class of radiopharmaceuticals for evaluation of region discrepancies in fatty acid metabolism which occur in ischemic heart disease and cardiomyopathies.
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